Field of the Invention
The present invention relates generally to compounds and methods for treating cancer. More specifically, the present invention relates to the inhibition mechanism of the urokinase receptor to treat cancer.
Background of the Invention
When a primary tumor metastasizes, the prospects for survival become substantially worse, resulting in approximately 90% death in patients.1 Metastasis occurs when cells from the primary tumor travel to distant sites and form new colonies. Cells escape from the primary tumors primarily through the circulatory system. These cells gain access to the vasculature as a result of multiple complex processes that involve invasion, migration, adhesion, and angiogenesis. A small number of cells that survive the voyage through the circulatory system arrive at new organ sites. Adhesion to and recognition of those sites in the endothelium is followed by re-entry through a process known as extravasation and result in the formation of a new tumor colony.
The urokinase receptor (uPAR) is a cell surface GPI-anchored protein that has been widely implicated with promoting metastasis. The receptor enhances pericellular proteolysis by serving as a docking site to the urokinase-type plasminogen activator (uPA), triggering a cascade of proteolytic events that include activation of plasminogen and matrix metalloproteinase (MMPs). The receptor also activates other cell signaling through lateral interactions with cell surface receptors that include integrins,2 receptor tyrosine kinases (RTKs).3,4 
The dual roles of the urokinase system in promoting degradation of the ECM and signaling have implicated the receptor with almost every step of tumor formation and progression, including tumorigenesis.5-11 